Ultraviolet B-induced and Nitric Oxide-mediated Cellular Signaling Circuit and Its Physiological Impacts
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Ohio University / OhioLINK
2010
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ndltd-OhioLink-oai-etd.ohiolink.edu-ohiou12821550112021-08-03T05:46:45Z Ultraviolet B-induced and Nitric Oxide-mediated Cellular Signaling Circuit and Its Physiological Impacts Wang, Lei Biochemistry Biology Biomedical Research Cellular Biology nitric oxide ultraviolet B zinc melanoma metastasis VLA-4 integrin <p>This dissertation is composed of two parts. In the first part, we focused on the molecular mechanism of ultraviolet B (UVB)-induced cell damage and the roles of nitric oxide (NO) and intracellular zinc in this process. We demonstrated that cell apoptosis, necrosis and skin tissue damage upon UVB-irradiation were mediated through the regulation of oxidative stress-related cellular signaling circuit. The activation of constitutive nitric oxide synthase (NOS) and generation of peroxynitrite (ONOO-) were shown as the causes of skin cell damage. UVB also induced an elevation of intracellular free Zn2+ within two minutes of exposure, which was dependent on the activation of cNOS and the production of peroxynitrite (ONOO-). We showed that the released free Zn2+ was not a cause of UVB-induced apoptosis since removal of free Zn2+ by a low concentration of Zn2+-specific chelator had no effects on UVB-induced apoptosis. However, a high concentration of the Zn2+ chelator was cytotoxic to cells and induced cNOS uncoupling. Our data suggest that oxidative stress causes intracellular free zinc release and induces cNOS uncoupling, which is critical for UVB-induced apoptosis.</p><p> In the second part, we characterized the expression level of very late antigen-4 (VLA-4, alpha4beta1) integrin modulated by UVB irradiation and the function of VLA-4 on melanoma metastasis after UVB irradiation. UVB is considered a significant risk factor and an indirect cause of melanoma formation. However, little is known about the potential effects of UVB in melanoma metastasis. The present data show that at 3 hours, 12 hours and 18 hours post-UVB irradiation, VLA-4 expression was unchanged relative to untreated cells, but adhesion to its endothelial ligand vascular cell adhesion molecule-1 (VCAM-1) decreased significantly. Further studies imply that the spatial organization of alpha4 subunit on the melanoma cell surface contributes to the changes in avidity for VCAM-1 upon UVB irradiation. Understanding of the molecular mechanism underlying melanoma-endothelia interactions upon UVB irradiation can guide the development of clinical treatments for melanoma.</p> 2010-09-23 English text Ohio University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1282155011 http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1282155011 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Biochemistry Biology Biomedical Research Cellular Biology nitric oxide ultraviolet B zinc melanoma metastasis VLA-4 integrin |
| spellingShingle |
Biochemistry Biology Biomedical Research Cellular Biology nitric oxide ultraviolet B zinc melanoma metastasis VLA-4 integrin Wang, Lei Ultraviolet B-induced and Nitric Oxide-mediated Cellular Signaling Circuit and Its Physiological Impacts |
| author |
Wang, Lei |
| author_facet |
Wang, Lei |
| author_sort |
Wang, Lei |
| title |
Ultraviolet B-induced and Nitric Oxide-mediated Cellular Signaling Circuit and Its Physiological Impacts |
| title_short |
Ultraviolet B-induced and Nitric Oxide-mediated Cellular Signaling Circuit and Its Physiological Impacts |
| title_full |
Ultraviolet B-induced and Nitric Oxide-mediated Cellular Signaling Circuit and Its Physiological Impacts |
| title_fullStr |
Ultraviolet B-induced and Nitric Oxide-mediated Cellular Signaling Circuit and Its Physiological Impacts |
| title_full_unstemmed |
Ultraviolet B-induced and Nitric Oxide-mediated Cellular Signaling Circuit and Its Physiological Impacts |
| title_sort |
ultraviolet b-induced and nitric oxide-mediated cellular signaling circuit and its physiological impacts |
| publisher |
Ohio University / OhioLINK |
| publishDate |
2010 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1282155011 |
| work_keys_str_mv |
AT wanglei ultravioletbinducedandnitricoxidemediatedcellularsignalingcircuitanditsphysiologicalimpacts |
| _version_ |
1719425131979210752 |